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Biomedical subjects

C D Walker

Publications and source records attributed to C D Walker.

49 records · Page 3Linked to original sources
PubMed1989

Central corticotropin-releasing factor administration prevents the excessive body weight gain of genetically obese (fa/fa) rats.

The genetic obesity of the fa/fa rat is due to or accompanied by perturbances in the autonomic nervous control of different target tissues (e.g. endocrine pancreas, brown adipose tissue). These disorders are likely to be secondary to central dysregulation(s), which could lie somewhere within or in relationship with the hypothalamus. In view of the reported effects of CRF in stimulating sympathetic nerve-mediated mechanisms, while inhibiting vagus nerve-mediated ones, ovine CRF (oCRF) was administered for 7 days into the cerebral ventricles of fa/fa rats at a dose (5 micrograms/day) that did not affect the pituitary-adrenal axis. oCRF treatment stopped the excessive weight gain of the obese animals; oCRF-treated animals gained only 1 g over 6 days, while the vehicle-treated ones gained 29 g (P = 0.044). The oCRF effect was unrelated to changes in food intake, as the two groups were pair-fed. oCRF-treated obese rats were characterized by a decrease in basal hyperinsulinemia, increases in brown adipose tissue weight and activity, and decreases in hepatic glycogen content and epididymal fat pad weight. It is suggested that intracerebroventricular oCRF administration to obese fa/fa rats prevents the 10-15% increase in body weight observed in vehicle-infused obese rats within 1 week by modulating the impaired autonomic nervous control of different target tissues. This does not occur in lean rats.

Adipose Tissue↗
PubMed1989

Differential activation of the pituitary-adrenocortical axis after stress in the rat: use of two genetically selected lines (Roman low- and high-avoidance rats) as a model.

We have examined the activation of the pituitary-adrenal axis in two lines of rats, the Roman high (RHA)- and low (RLA)-avoidance rats known to be emotionally different. These rats are selected for rapid acquisition of a conditioned avoidance response (RHA) compared with failure to acquire this response (RLA). In this study the endocrine response (ACTH, corticosterone, aldosterone) of RLA and RHA rats to two types of stress was examined: exposure to open-field stress for 10 min (Op) or exposure to ether vapours for 3 min (E). Basal plasma ACTH concentrations were lower in RLA than in RHA rats (RLA: 110.8 +/- 24.5 ng/l; RHA: 252.7 +/- 60.8 ng/l, P less than 0.05) but the absolute values of ACTH reached after both types of stress were comparable between RLA and RHA rats. Plasma corticosterone and aldosterone under resting conditions were not different between RLA and RHA rats. Plasma corticosterone was higher in RLA following openfield stress (P less than 0.05) while no differences between RLA and RHA were observed after ether stress (RHA: basal = 66 +/- 14.nmol/l, Op = 384 +/- 55, E = 606 +/- 75; RLA: basal = 121 +/- 52, Op = 612 +/- 92, E = 698 +/- 89). Stress-induced increases in plasma aldosterone were higher in the RLA line after both types of stress (RHA: basal = 175 +/- 36 pmol/l, Op = 546 +/- 53, E = 563 +/- 47; RLA: basal = 272 +/- 64, Op = 1246 +/- 91, E = 863 +/- 72).

Adrenal Cortex↗
PubMed1988

Effects of early undernutrition and handling on the adrenocortical activity of neonatal rats.

Early neonatal experiences such as handling or undernutrition may alter developmental patterns associated with brain maturation and neuroendocrine regulation. Therefore, we tested neonatal ACTH and corticosterone responses to ether stress in pups submitted to chronic underfeeding which involves daily handling (U), daily handling only (H), or no handling (I). Pituitary ACTH content and brain myelin basic protein (MBP) content were measured in all rat groups. We found that the order of magnitude in stress-induced ACTH secretion was: I greater than H greater than U on day 14 and 18 of age while on day 10, only a small significant response in the H group was observed. Corticosterone secretion after stress was increased on day 14 in both H and I rats while no response was observed in the U group at all ages. Pituitary ACTH content of U pups was significantly (p less than 0.01) reduced compared to H rats on day 10 of age but not later. Underfeeding had profound effects on MBP synthesis of U rats since brain MBP content on day 14 was 5-fold lower in U versus H pups. In addition, handling enhanced MBP production since H rats exhibited higher (p less than 0.05) MBP content as compared to I rats. Thus, both handling and undernutrition experienced early in life are able to affect central brain maturation as well as neonatal adrenocortical responses to stress.

Adrenal Cortex↗
PubMed1986

Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus.

The neonatal rat shows a period of decreased responsiveness to noxious stimuli during the first 3 weeks of life, but the nature of this impairment is still controversial. To test the functionality of the hypothalamus-pituitary-adrenal axis during this period, we studied pituitary and adrenal responsiveness to exogenous ovine CRF and the ability of various stressors (ether vapors, electroshocks, and hypoxia) to elicit ACTH and corticosterone secretion. We also measured hypothalamic CRF content and pituitary ACTH content as well as CRF-binding sites in the anterior pituitary. From days 3-10, small elevations in plasma ACTH and corticosterone levels were observed after a 3-min exposure to ether vapors or electroshocks. In contrast, during this period, a 20-min exposure to hypoxia (5% O2 in N2) was unable to trigger measurable ACTH secretion, while corticosterone was significantly elevated. From days 14-21, plasma ACTH and corticosterone levels increased significantly after exposure to ether stress, hypoxia, and, to a lesser extent, electroshocks. By contrast, administration of urethane (1.2 g/kg BW) caused a significant increase in ACTH secretion on days 3, 5, and 10, an effect that was partially suppressed by pretreatment with an anti-CRF serum. This suggests that endogenous CRF can be released by at least some stimuli as early as day 3. Direct stimulation of the pituitary with synthetic oCRF (10 micrograms/kg BW) caused significant elevations in plasma ACTH levels at all ages tested (days 3 through 21), though these increases were significantly (P less than or equal to 0.01) smaller on day 3 (2.7-fold) than on day 21 (4.3-fold). Hypothalamic CRF content as well as ACTH content increased gradually with age, but the values reached by the third week of life were still low compared to the values on day 45. Finally, anterior pituitary CRF-binding sites averaged 317 +/- 48 fmol/mg protein on day 5 and 158 +/- 22 fmol/mg protein on day 17. The affinity (Kd) of the receptor for CRF was not significantly different on day 5, 17, or 45. These results show that although pituitary corticotrophs appear to be functional at birth, exposure to stress does not elicit marked increases in plasma ACTH until day 14 of age.

Adrenal Glands↗
PubMed1986

Increased pituitary sensitivity to glucocorticoid feedback during the stress nonresponsive period in the neonatal rat.

Neonatal rats show a diminished response to stress [the stress-nonresponsive period (SNRP)] from day 2-3 until day 14 of age; the physiological bases for the SNRP are unknown. We examined whether enhanced sensitivity of the brain or pituitary to the inhibitory feedback effects of circulating glucocorticoids (GC) contributes to the SNRP. Age-related changes in the ability of corticosterone (CORT) and dexamethasone (DEX) to inhibit the ACTH secretion induced by urethane or CRF were studied. We also examined the ACTH response to ether stress or CRF in intact or 24 h-adrenalectomized 5-day-old rats. Plasma ACTH did not increase in intact rats after ether stress (basal: 64.6 +/- 9.1 pg/ml vs. stressed: 66.8 +/- 8.9 pg/ml; P greater than 0.05), whereas small elevations occurred after CRF challenge (184.6 +/- 40 pg/ml; P less than or equal to 0.01). Five-day-old adrenalectomized rats, which had elevated basal ACTH concentrations, increased ACTH secretion after exposure to ether or CRF. Thus, negative feedback appears to mediate critically the SNRP. Furthermore, sensitivity to such feedback was enhanced during the SNRP since the capacity of CORT to inhibit urethane-induced ACTH secretion in vivo declined with age; 1 mg/kg BW was the minimal dose that inhibited ACTH secretion at day 10, whereas at day 18, the threshold for a similar inhibition was 5 mg/kg BW. In contrast, at both ages, a dose of 10 micrograms/kg BW DEX inhibited ACTH release. In vitro dose response studies in whole pituitaries further demonstrated the enhanced pituitary sensitivity to GC feedback during the SNRP since the IC50 for CORT inhibition of CRF-induced ACTH release increased from days 3-5 to days 22-23. A similar, although not statistically significant trend was observed for DEX inhibition. Thus, neonatal rats exhibit an enhanced pituitary sensitivity to GC during the SNRP and removal of this inhibition allows ACTH secretion in response to ether stress.

Adrenalectomy↗
PubMed1985

Effects of Ni Deficiency on Some Nitrogen Metabolites in Cowpeas (Vigna unguiculata L. Walp).

Cowpeas grown in nutrient solutions, from which Ni had been removed by a ligand exchange technique, accumulated urea in most tissues. Urea levels were highest (up to 3.1 percent dry weight) in necrotic leaf tips. Urea accumulation in Ni-deficient cowpea tissues amounted to about 1 percent of the total N. The accumulation of urea was presumably associated with the catabolism of N compounds in older tissues and the redistribution of N catabolites within the plant during the reproductive growth. The exclusion of N salts from the nutrient media at a late stage of growth, either with or without added Ni, led to a general amelioration of urea accumulation and a lower level of the related amino acid, arginine, in root and stem tissue. Plant leaves that contained toxic levels of urea and displayed necrotic symptoms had tissue Ni levels ranging from less than 0.01 to 0.15 mug Ni per gram dry weight. Nickel concentrations in tissue from plants not treated with Ni, were initially very low, but increased as the cowpeas matured. Apparently, there was a source of Ni contamination in the Ni-deficient growth media which provided a source of Ni for uptake by the plants during growth. Ureide levels were low and unaffected by Ni deprivation. No evidence for free purines or uric acid accumulation in plant tissues could be found. It is hypothesized that Ni (and urease) participates in the normal N metabolism of these plants during the reproductive phase of growth.

Journal Article↗
PubMed1979

Protein degradation in metabolic and nutritional disorders.

The increased protein degradation associated with diabetes appears to be different in many respects from protein catabolism in normal, well-nourished cells. In all normal eukaryotic cells examined, degradation of cytosolic proteins exhibits several striking features. Large proteins tend to be degraded more rapidly than small proteins, acidic proteins tend to be degraded more rapidly than neutral or basic proteins, and glycoproteins are degraded more rapidly than non-glycoproteins. Furthermore, a general correlation exists between protein half-life in vivo and susceptibility to proteolytic attack in vitro. In streptozotocin-diabetic rats the relationships between degradative rate and protein size, net charge, and carbohydrate content are absent or markedly reduced among cytosolic proteins of the liver. However, the correlation between protein half-life and susceptibility to proteinase in vitro is unaltered. Therefore, the enhanced protein degradation in diabetes shows little or no selectivity towards large, acidic, glycoproteins but does show specificity for proteins than tend to be sensitive to proteinases. Similar studies using other tissues from diabetic rats are reported and general characteristics of the enhanced liver protein catabolism in starvation and hyperthyroidism are briefly discussed. The biochemical reasons for the increased protein catabolism in diabetes are unclear although several possible explanations are presented. The enhanced breakdown is probably not due to cellular proteins becoming more proteinase sensitive in diabetes since experiments with a variety of endoproteinases including pronase, chymotrypsin, pepsin, and lysosomal cathepsins have failed to demonstrate more rapid digestion of liver proteins from diabetic animals.

Animals↗
PubMed1978

Polyamine and magnesium effects on mitochondrial respiration in control and heat-acclimated rats.

Studies were made of polyamine and Mg++ effects on rat liver mitochondrial alpha ketoglutarate oxidase (alphaKGO) and succinoxidase (SO). High spermidine levels suppress S3 and S4 of alphaKGO at 0.6-1.17 mM Mg++: some combinations of it and Mg++ increase the respiratory control ratio (RCR). Spermine suppresses S4 of alphaKGO and increases the RCR but suppresses the RCR of SO at high levels. In heat-acclimated (HA) animals in which we have studied only spermine effects on alphaKGO, RCRs of HA rats are greatly increased compared to those of controls.

Acclimatization↗
PubMed1978

General characteristics of protein degradation in diabetes and starvation.

The enhanced protein degradation associated with diabetes and starvation is fundamentally different from normal protein catabolism. In normal eukaryotic cells large molecular weight proteins tend to be degraded more rapidly than small proteins, acidic proteins tend to be degraded more rapidly than neutral or basic proteins, and glycoproteins tend to be degraded more rapidly than nonglycoproteins. All three of these general correlations are absent or markedly reduced in liver and muscle of diabetic and starved rats. In contrast, the correlations between proteins size and half-life, between protein net charge and half-life, and between protein carbohydrate content and half-life are not affected in brain of diabetic or starved animals. These results suggest that diabetes and starvation alter the general characteristics of intracellular protein degradation in target tissues of insulin. Degradation of serum proteins is also affected in diabetes and starvation. In normal animals a general correlation exists between isoelectric points of serum proteins and their degradative rates. This relationship is abolished in diabetes and starvation, as it is among liver and muscle proteins. The implications of our findings are discussed with regard to possible mechanisms of the enhanced protein breakdown.

Animals↗